MesenSistem-EB: systemic haploidentical mesenchymal stem cell therapy in recessive dystrophic epidermolysis bullosa associated with clinical benefits and correlated with MCP1 and sCD40L dynamics.

Background: Recessive dystrophic epidermolysis bullosa (RDEB) is a devastating genodermatosis caused by biallelic Methods: Phase I/II, single-center, open-label trial, in which nine children with severe RDEB were recruited and eight completed the study after three intravenous infusions of haploidentical BM-MSC (2-3×10 Results: MSC therapy was well-tolerated without serious adverse events. Long-term pruritus, sleep and fatigue were globally reduced. In 7/8 patients at least one key domain significantly improved (disease severity, pruritus, or inflammation) with five classified as good responders. Global median CRP and fibrinogen levels remained stable throughout the study period. Responses correlated with sCD40L and MCP1 dynamics. Flow cytometry revealed altered circulating myeloid and lymphoid compartments at baseline. Post-infusion, immune cell subset changes did not consistently distinguish responders while typically including increased CLA expression on monocytes, partial recovery of memory CD8 Conclusions: BM-MSC is a safe and potentially effective anti-inflammatory intervention that mitigates the expected escalation of systemic inflammatory markers during a critical phase of RDEB progression. MCP1 and sCD40L modulation, with both potentially serving as predictive biomarkers. MSC appear to exert both shared and patient-specific immunomodulatory effects depending on baseline inflammatory cues. Findings provide insights into individual variability, underlying mechanisms and potential therapeutic responsiveness, supporting their use also as a complementary strategy. Clinical trial registration: ClinicalTrials.gov, identifier NCT04153630.